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AstraZeneca Initiates CDx Partnerships with Roche, Qiagen

AstraZeneca today said it launched a pair of companion diagnostics collaborations related to two drugs for non-small-cell lung cancer (NSCLC), saying it would work with Roche to develop a plasma-based test to support its investigational compound AZD9291, and also team up with Qiagen on a non-invasive diagnostic test to identify patients with the disorder who are suitable for treatment with the European-approved treatment Iressa® (gefitinib).

The value of both collaborations was not disclosed.

AstraZeneca said the diagnostic it would co-develop with Roche will be designed to identify epidermal growth factor receptor (EGFR) mutations in both tumor tissue and plasma derived from patients with NSCLC. The test will also be designed to optimize the clinical development of AZD9291 for patients who are resistant to first-generation EGFR tyrosine kinase inhibitors (TKIs).

A new diagnostic test based on circulating DNA (ctDNA) in plasma samples would provide an alternative method of identifying the resistance mutation, called T790M, in patients in whom the disease has progressed despite treatment with EGFR-TKIs. At present, these patients are subject to repeat biopsies.

“Understanding the nature of each individual’s tumor and therefore which medicine is most likely to benefit them is vital if we are to transform the way cancer patients are diagnosed and treated,” Mondher Mahjoubi, svp, global product strategy for oncology at AstraZeneca, said in a statement.

In some cases, collecting enough tissue for testing is not possible, added Paul Brown, head of Roche Molecular Diagnostics: “This collaboration will enable molecular testing through plasma specimens and provide the information needed to inform treatment decisions without the complications of surgery, consequently increasing the level of care clinicians can give to the patient.”

AZD9291 is a highly selective, irreversible inhibitor of both the activating sensitizing EGFR mutation (EGFRm+) and T790M, while sparing the activity of wild type EGFR. In an ongoing Phase I study, AstraZeneca said, AZD9291 has shown early evidence of activity as a once-daily monotherapy with clinical responses observed in an EGFRm+ population of patients with NSCLC who have previously failed on EGFR TKIs and also in patients with the T790M mutation. To date, AZD9291 has been well-tolerated with low rates of side effects, the company added.

Patients with EGFRm+ NSCLC are particularly sensitive to treatment with currently available EGFR TKIs, which block the cell signaling pathways that drive the growth of tumor cells. However, tumor cells almost always develop resistance to treatment, leading to disease progression. In approximately half of patients, this resistance is caused by T790M, yet no targeted therapies are now approved for treating tumors with the mutation.

With Qiagen, a longtime partner, AstraZeneca said it will co-develop a test to identify patients that can be treated with Iressa, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that blocks the signals from the EGFR, leading to tumor growth. Iressa is approved in 65 countries—including the nations of the European Union, where it is indicated for the treatment of adults with locally advanced or metastatic NSCLC with activating mutations of EGFR-TK across all lines of therapy.

The test uses a highly sensitive assay to detect EGFR mutations in the small fragments of ctDNA in plasma taken from patients’ blood samples. AstraZeneca and Qiagen said the test has demonstrated robust and reliable identification of EGFR mutation status using samples from the Phase IV IRESSA Follow Up Measure (IFUM) study. The companies are seeking approval from the European Medicines Agency for the ctDNA test, as a companion diagnostic for IRESSA.

Since EGFR is a protein found in abnormally high levels on the surface of NSCLC cells, the companies reason that their blood test will enable doctors to identify patients who have the EGFR mutation, and thus are likely to benefit most from treatment with Iressa. At present, the collection of tumor tissue, by needle biopsy or during resection, serves as the chief current method of assessing EGFR mutation status.

“The use of circulating tumor DNA testing will allow doctors to target the individual needs of each patient quickly and accurately,” Mahjoubi stated.

Added Qiagen CEO Peer M. Schatz: “Liquid biopsies are an exciting new field in sample technology and an area of core leadership for Qiagen. We are rapidly expanding our portfolio in this field and are seeing a broad uptake of our new standards.”

The AstraZeneca partnership is the latest of several recent moves by Qiagen to co-develop blood-based diagnostics, either on its own or as companion diagnostics to drugs developed by biopharma partners.

Just four days ago on Thursday, Qiagen was awarded an exclusive global license from the University of Tokyo to develop assays for SF3B1 mutations, including next-generation sequencing (NGS) gene panels, for blood cancers. These mutations may indicate a favorable prognosis for patients with bone marrow disorders called myelodysplastic syndromes, Qiagen said. The licensing agreement, whose value was not disclosed, also included three additional spliceosome biomarkers implicated in various blood cancers and targeting variants in the U2AF35 (U2AF1), ZRSR2 and SFRS2 genes.

Last month, the FDA approved Qiagen’s artus CMV RGQ MDx Kit, a PCR-based assay designed to monitor viral load in patients with cytomegalovirus (CMV), with results available in up to four hours. And in May, the FDA gave premarket approval (PMA) to Qiagen’s third companion diagnostic paired with a new medicine, the therascreen KRAS RGQ PCR Kit for the KRAS mutation, intended to guide the treatment of metastatic colorectal cancer patients with Amgen's Vectibix® (panitumumab).

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